4-Methoxybenzoic Acid → N,4-Dimethoxy-N-methylbenzamide

To a stirred solution of 4-methoxybenzoic acid (10.0 g, 65.70 mmol) in DCM (50 mL) were added EDCI (18.90 g, 98.60 mmol), HOBT (10.0 g, 65.70 mmol), N-methoxy methylamine (13.0 g, 131.40 mmol) and DIPEA (34.3 mL, 197.20 mmol) at RT under a nitrogen atmosphere. The reaction mixture was stirred at RT for 12 h. The reaction mixture was diluted with water and the aqueous layer was extracted with DCM (3×100 mL). The combined organic extracts were washed with water (2×100 mL), brine (2×50 mL), dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure to afford crude product. The crude material was purified by flash column chromatography using 20% ethyl acetate in hexane and silica gel (230-400 Mesh) to afford N,4-dimethoxy-N-methylbenzamide (11.0 g, 86%) as a colorless liquid.

1. extractionthe aqueous layer was extracted with DCM (3×100 mL)
2. washThe combined organic extracts were washed with water (2×100 mL), brine (2×50 mL)
3. dry with materialdried over anhydrous Na2SO4
4. filtrationfiltered
5. customevaporated under reduced pressure
6. customto afford crude product
7. customThe crude material was purified by flash column chromatography

ORD record

ord-6560f5611a5d444e86ea47005262a58a

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08946222B2